Gas exchange is the primary function of the pulmonary circulation. Therefore, it would be advantageous if this function were to be achieved with minimal energy expenditure. Because of the pulsatility of the pulmonary circulation, wave reflection in the pulmonary arterial tree is inevitable. Wave reflection is important because it has an adverse effect on the hydraulic power that is delivered into the main pulmonary artery (MPA) from the right ventricle. Previous work indicates that characteristic impedance is an important determinant of wave reflection and altered by neurohumoral mechanisms. Therefore modulation of characteristic impedance may represent a way of controlling wave reflection. Characteristic impedance is dependent on the dimensions and the elasticity of the MPA. The dimensions of the MPA depend not only on transmural pressure, but also on flow. It is generally believed that the increased blood flow is detected by the increased shear rate on the endothelium. Therefore endothelial dependent mechanisms may be involved in the regulation of wave reflection. The overall objective of the proposed work is to determine the mechanisms involved that control the dimensions and elasticity of the MPA. It is proposed to measure the pressure, diameter and length of a segment of MPA in both awake and anesthetized dogs so that changes of dimensions and elasticity of this vessel can be calculated. The specific aims of this project are as follows: (1) to determine the independent effects of pressure and flow on both the elasticity and the dimensions of the MPA, and the extent to which they are modulated by increased smooth muscle tone, autonomic receptors, cyclooxygenase products and nitric oxide production in anesthetized dogs; (2) to determine the role of autonomic receptors, cyclooxygenase products and nitric oxide production on the MPA during an acute circulatory disturbance in awake dogs, (3) to determine the relation between the changes of dimensions and elasticity of the MPA due to increased pulmonary vascular tone; and (4) to determine the effects of anesthesia on endothelial dependent mechanisms in the MPA. It is hoped that the results of these experiments ultimately will lead to the identification of therapeutic modalities to minimize the deleterious effects of wave reflection on pulmonary hemodynamics in lung disease.